The U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for EYLEA® (aflibercept) Injection for the treatment of diabetic retinopathy in patients with diabetic macular edema (DME). Under the Prescription Drug User Fee Act (PDUFA), the goal for a priority review is six months, for a target action date of March 30, 2015.
In September 2014, the FDA granted EYLEA® (aflibercept) Injection Breakthrough Therapy designation for the treatment of diabetic retinopathy in patients with DME. The FDA created the Breakthrough Therapy designation to expedite the development and review of drugs for serious or life-threatening conditions. A Breakthrough Therapy drug must show preliminary clinical evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy.
The Phase 3 VIVID-DME and VISTA-DME trials, which supported the approval of EYLEA in DME, included a pre-specified secondary endpoint evaluating diabetic retinopathy based on an established grading scale in patients with DME. The two-year results from these trials on the primary endpoint of best-corrected visual acuity (BCVA) and overall safety have been previously reported.
EYLEA® (aflibercept) Injection is available as a single, 2 milligram (mg) strength intravitreal injection for all approved indications. EYLEA is approved in the U.S. for the treatment of wet age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), and DME.
About the VIVID-DME and VISTA-DME Trials
The Phase 3 VISTA-DME and VIVID-DME studies of 862 patients compared EYLEA 2 mg given monthly, EYLEA 2 mg given every two months (after five initial monthly injections), or macular laser photocoagulation (at baseline and then as needed). In the DME studies, at one year, the mean changes in Best Corrected Visual Acuity (BCVA), as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart for the monthly and every two month EYLEA groups, were statistically significantly improved compared to the control group and were similar to each other. Across both trials at one year, patients in both EYLEA dosing groups gained, on average, the ability to read approximately two additional lines on an eye chart compared with almost no change in the control group. A secondary endpoint of the trials was the proportion of patients who achieved a 2-step or greater improvement on the ETDRS diabetic retinopathy (DR) severity scale at two years.
In these trials, EYLEA had a similar overall incidence of adverse events (AEs), ocular serious AEs, and non-ocular serious AEs across treatment groups and the control group. Arterial thromboembolic events as defined by the Anti-Platelet Trialists’ Collaboration (non-fatal stroke, non-fatal myocardial infarction, and vascular death) also occurred at similar rates across treatment groups and the control group. The most frequent ocular treatment emergent AEs (TEAEs) observed in the VISTA-DME and VIVID-DME trials included conjunctival hemorrhage, eye pain, cataract, and vitreous floaters. The most common nonocular TEAEs included hypertension and nasopharyngitis, which occurred with similar frequency in the treatment groups and the control group.
About EYLEA® (aflibercept) Injection for Intravitreal Injection
EYLEA is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. EYLEA is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. EYLEA helps prevent VEGF-A and PLGF from interacting with their natural VEGF receptors as shown in preclinical studies.